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Öğe The Association of Minor Congenital Anomalies and Childhood Cancer(Wiley, 2011) Durmaz, Asude; Durmaz, Burak; Kadioglu, Bengu; Aksoylar, Serap; Karapinar, Deniz; Koturoglu, Guldane; Orman, Mehmet N.; Özkınay, Ferda; Cogulu, OzgurBackground. Although the association of some congenital malformations and specific genetic syndromes is well understood, the association between minor anomalies and cancer is not well known. In recent years some researchers have reported studies establishing this association in different types of cancer. In this study, we aimed to investigate the prevalence and patterns of age-independent minor anomalies in childhood cancer patients. Procedure. Two hundred patients with various types of cancer and 200 healthy controls were examined by two different medical geneticists for minor anomalies who evaluated all the cases and controls simultaneously. Besides minor anomalies, information on the consanguinity between the parents and occurrence of cancer in relatives were also recorded. The types of minor anomalies in different types of cancer, the number of minor anomalies in patients and controls, the association between cancer and the occurrence of different types of minor anomalies were also evaluated. Results. The consanguinity and the history of cancer in relatives were significantly more prevalent in patients (P = 0.04 and P < 0.001, respectively). The number of minor anomalies in patients were significantly higher compared to the controls (P < 0.01). Particularly, the presence of hypertelorism, high-arched palate (approximately 40-fold higher, 95% CI: 12.895-125.037) and hand-foot anomalies were found to be more prevalent in patients having cancer compared to the controls. Conclusion. The common pathways during the embryogenesis may play a role in the development of cancer. The presence and the combination of minor anomalies seem to be associated with a higher prevalence of cancer. Pediatr Blood Cancer 2011;56:1098-1102. (C) 2011 Wiley-Liss, Inc.Öğe BERNSTEIN POLYNOMIAL APPROACH AGAINST TO SOME FREQUENTLY USED GROWTH CURVE MODELS ON ANIMAL DATA(Isoss Publ, 2010) Gurcan, Mehmet; Colak, Cemil; Orman, Mehmet N.Non-linear Logistic, Gompertz and Richards growth curve models were fitted to the data from Simmental x Southern Anatolian Red (SAR) crossbred cattles. Individual growth curves were fitted based on live weight measurements, and then general growth curves were obtained for all the models. In addition, Bernstein basis polynomials have played important roles in nonparametric curve estimation. Therefore, Bernstein polynomial approach was used to model the growth curve in the current data. We determined the accuracy of the models by using coefficient of determination (R(2)), Mean square error (MSE) and iteration number together. In summary, the most suitable model based on the accuracy criteria was Bernstein model. Among the well-known growth curves, Logistic, Richards and Gompertz were ordered respectively.Öğe Coexistence of atrioventricular accessory pathways and drug-induced type 1 Brugada pattern(Wiley, 2018) Hasdemir, Can; Juang, Jimmy Jyh-Ming; Kose, Sedat; Kocabas, Umut; Orman, Mehmet N.; Payzin, Serdar; Sahin, Hatice; Celen, Candan; Ozcan, Emin E.; Chen, Ching-Yu Julius; Gunduz, Ramazan; Turan, Oguzhan E.; Senol, Oktay; Burashnikov, Elena; Antzelevitch, CharlesBackgroundAtrial arrhythmias, particularly atrioventricular nodal reentrant tachycardia, can coexist with drug-induced type 1 Brugada electrocardiogram (ECG) pattern (DI-Type1-BrP). The present study was designed to determine the prevalence of DI-Type1-BrP in patients with atrioventricular accessory pathways (AV-APs) and to investigate the clinical, electrocardiographic, electrophysiologic, and genetic characteristics of these patients. MethodsOne-hundred twenty-four consecutive cases of AV-APs and 84 controls underwent an ajmaline challenge test to unmask DI-Type1-BrP. Genetic screening and analysis was performed in 55 of the cases (19 with and 36 without DI-Type1-BrP). ResultsPatientswith AV-APs were significantly more likely than controls to have a Type1-BrP unmasked (16.1vs 4.8%, P=0.012). At baseline, patients with DI-Type1-BrP had higher prevalence of chest pain, QR/rSr' pattern in V-1 and QRS notching/slurring in V-2 and aVL during preexcitation, rSr' pattern in V-1-V-2, and QRS notching/slurring in aVL during orthodromic atrioventricular reentrant tachycardia (AVRT) compared to patients without DI-Type1-BrP. Abnormal QRS configuration (QRS notching/slurring and/or fragmentation) in V-2 during preexcitation was present in all patients with DI-Type1 BrP. The prevalence of spontaneous preexcited atrial fibrillation (AF) and history of AF were similar (15%vs 18.3%, P=0.726) in patients with and without DI-Type1-BrP, respectively. The prevalence of mutations in Brugada-susceptibility genes was higher (36.8%vs 8.3%, P=0.02) in patients with DI-Type1-BrP compared to patients without DI-Type1-BrP. ConclusionsDI-Type1-BrP is relatively common in patients with AV-APs. We identify 12-lead ECG characteristics during preexcitation and orthodromic AVRT that point to an underlying type1-BrP, portending an increased probability for development of malignant arrhythmias.Öğe Comparison of Five Survival Models: Breast Cancer Registry Data from Ege University Cancer Research Center(Ortadogu Ad Pres & Publ Co, 2010) Hayat, Elvan Akturk; Suner, Asli; Uyar, Burak; Dursun, Omer; Orman, Mehmet N.; Kitapcioglu, GulObjective: In this study, we aimed to compare the results of the survival analysis of the patients with breast cancer using Weibull, Gamma, Gompertz, Log-Logistic and Log-Normal parametric models. Material and Methods: The data obtained from 5457 patients with breast cancer from Ege University Cancer Research Centre between 1992 and 2007 was used in this study. The patients were divided into two groups with respect to their ages, they were divided into two groups as 49 and below and 50 and above. The Log rank test was applied to compare the survival curves of the two age groups obtained by Kaplan Meier method. A survival analysis was conducted by using Weibull, Gamma, Gompertz, Loglogistic and Lognormal distribution of parametric models. Results: Survival curves of two groups were compared by using a log-rank test and no statistical significant difference was found between the two groups. In the analysis of the survival periods using parametric models, the age variable is taken as the covariate. To determine the best model among parametric models, Akaike Information Criteria (MC) was exploited. The results of the study revealed that the survival model found by the Gompertz distribution was the most appropriate one. Conclusion: By using AIC, the models obtained via Weibull, Loglogistic, Lognormal, Gamma and Gompertz were compared and the most suitable model for the obtained data distribution was determined. Although the AIC values for the five distributions in question were very close to each other, the Gompertz distribution, which had the lowest AIC value, was determined as the most suitable model.Öğe Dosing-time, feeding, and sex-dependent variations of everolimus pharmacokinetics in mice(Wiley, 2024) Ozturk Civelek, Dilek; Ozturk Seyhan, Narin; Akyel, Yasemin Kubra; Gazioglu, Isil; Pala Kara, Zeliha; Orman, Mehmet N.; Okyar, AlperBackgroundEverolimus is an oral mammalian target of rapamycin (mTOR) inhibitor used as an immunosuppressant and anticancer. Its pharmacokinetics is highly variable, it has a narrow therapeutic window and shows chronotoxicity with the best time at ZT13 and worst time at ZT1 (ZT; Zeitgeber time, time after light onset) in the preclinical setting.ObjectivesIn the present study, we aimed to investigate whether the pharmacokinetics of everolimus vary according to dosing time and whether sex and feeding status interfere with the chronopharmacokinetics.MethodA single dosage of 5 mg/kg everolimus was administered orally to C57BL/6J male and female mice, in fed or fasted states at ZT1-rest and ZT13-activity times and blood and tissue samples were collected at 0.5, 1, 2, 4, 12, and 24 h following drug administration. Ileum, liver, plasma, and thymus concentrations of everolimus were determined.ResultsFemales had a greater ileum AUC0-24h than males when fed (P = 0.043). Everolimus AUC0-24h in the liver was substantially greater at ZT1 than at ZT13 in a fasted state (P = 0.001). Plasma Cmax, AUC0-24h, and AUCtotal were not statistically significant between the groups (P = 0.098). In one of the target organs of everolimus, the thymus, males had considerably higher amounts at ZT1 than females (P = 0.029).ConclusionOur findings imply that the pharmacokinetics of everolimus in mice may differ according to dosing time, sex, and feeding. Greater tissue distribution of everolimus at ZT1 may be associated with the worst tolerated time of everolimus. Our research suggests that oral chronomodulated everolimus therapy may be more effective and safer for cancer patients.Öğe Effect of Coronary Thrombus Aspiration in Non ST Elevation Acute Coronary Syndrome Patients on Three-Year Survival- Does it add any Benefit?(Sage Publications Inc, 2022) Yildiz, Bekir S.; Cetin, Nurullah; Gunduz, Ramazan; Bilge, Adnan; Ozgur, Su; Orman, Mehmet N.We assessed the effect of thrombus aspiration (TA) during percutaneous coronary intervention (PCI) on in-hospital and 3-year mortality in consecutive non-ST segment elevation myocardial infarction (n = 189) and unstable angina pectoris (n = 148) patients (n = 337) between 2011 and 2016. In total, 153 patients (45.4%) underwent TA. The number of patients with postoperative thrombolysis in terms of myocardial infarction grade 3 blood flow (P < .001) and myocardial blush grade 3 (P < .001) were significantly higher in all TA groups. At 6-, 12- and 24-month post-PCI, the mean left ventricular ejection fraction was significantly higher in the all TA groups versus the stand alone PCI group (P < .001). Thrombus aspiration was associated with a significant improvement both in epicardial flow, myocardial perfusion and left ventricular ejection fraction. Thrombus aspiration during PCI in all acute coronary syndrome (except ST segment elevation) patients was associated with better survival compared with stand alone PCI group at 3-year follow-up (P = .019).Öğe Electrocardiographic variables associated with underlying Brugada syndrome or drug-induced Type 1 Brugada pattern in patients with slow/fast atrioventricular nodal reentrant tachycardia(Wiley, 2022) Hasdemir, Can; Sahin, Hatice; Duran, Gulten; Orman, Mehmet N.; Kocabas, Umut; Payzin, Serdar; Aydin, MehmetBackground: The coexistence of clinical atrioventricular nodal reentrant tachycardia (AVNRT) and drug-induced type 1 Brugada pattern (DI-Type 1 BrP) has been previously reported. The present study was designed to determine the 12-lead ECG characteristics at baseline and during AVNRT and to identify a subset of 12-lead ECG variables of benefit associated with underlying Brugada syndrome (BrS)/DI-Type 1 BrP among patients with slow/fast AVNRT. Methods: A total of 40 (11 numerical/29 categorical) 12-lead ECG parameters were analyzed and compared between patients with (n = 69) and without (n = 104) BrS/DI-Type1-BrP matched for age, female gender, body mass index, left ventricular ejection fraction and comorbid conditions. Five distinct types of ECG pattern (Type A/B/C/D/E) in V1-V2 leads during AVNRT were defined. Results: A total of nine electrocardiographic variables, four at baseline, and five during AVNRT were identified. At baseline, patients with BrS/DI-Type 1 BrP had higher prevalence of interatrial block, leftward shift of frontal plane QRS axis, the absence of normal QRS pattern (the presence of rSr' pattern or type 2/3 Brugada pattern) in V1-V2 and QRS fragmentation in inferior leads compared to patients without BrS/DI-Type 1 BrP. During AVNRT, patients with BrS/DI-Type 1 BrP had higher prevalence of Type A ECG pattern (coved-type ST-segment elevation) in V1-V2, Type C ECG pattern (pseudo-r' deflection in V-1 and RBBB-like pattern in V-2), pseudo-r' deflection in V-1, QRS fragmentation in inferior leads and isolated QRS fragmentation/notching/slurring in aVL compared to patients without BrS/DI-Type 1 BrP. Conclusions: We identify several electrocardiographic variables that point to an underlying type 1 BrP among patients with slow/fast AVNRT.Öğe Frequency of Irritable Bowel Syndrome in Patients with Brugada Syndrome and Drug-Induced Type 1 Brugada Pattern(Excerpta Medica Inc-Elsevier Science Inc, 2021) Sarica, Anil S.; Bor, Serhat; Orman, Mehmet N.; Barajas-Martinez, Hector; Juang, Jyh-Ming Jimmy; Antzelevitch, Charles; Hasdemir, CanIrritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Prevalence of FBDs over a 12 months period were compared between probands with BrS/ drug-induced type 1 Brugada pattern (DI-Type 1 BrP) (n = 148) and a control group (n = 124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type 1 BrP and 8.1% in the control group (p = 2.34 x 10(-4)). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p = 0.033) was a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/ DI-Type 1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. In conclusion, IBS is a common co-morbidity in patients with BrS/DI-Type 1 BrP. Presence of current and/or history of migraine are a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type 1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype. (C) 2021 Elsevier Inc. All rights reserved.Öğe Optimization of prednisolone acetate-loaded chitosan microspheres using a 2(3) factorial design for preventing restenosis(Informa Healthcare, 2010) Sarisozen, Can; Arica, Betuel; Orman, Mehmet N.; Hincal, A. Atilla; Calis, SemaPrednisolone acetate (PA)-loaded microspheres were prepared by the spray-drying technique using different polymer (1% and 2%) and drug concentrations (10% and 20%). To obtain the optimum formulation, a three-factor two-level (2Öğe Recognition and clinical implications of high prevalence of migraine in patients with Brugada syndrome and drug-induced type 1 Brugada pattern(Wiley, 2020) Hasdemir, Can; Gokcay, Figen; Orman, Mehmet N.; Kocabas, Umut; Payzin, Serdar; Sahin, Hatice; Antzelevitch, CharlesIntroduction We have previously reported high 1-year prevalence of migraine in patients with atrial arrhythmias associated with DI-type 1 BrP. the present study was designed to determine the lifetime prevalence of migraine in patients with Brugada syndrome (BrS) or drug-induced type 1 Brugada pattern (DI-type 1 BrP) and control group, to investigate the demographic and clinical characteristics, and to identify clinical variables to predict underlying BrS/DI-type 1 BrP among migraineurs. Methods and Results Lifetime prevalence of migraine and migraine characteristics were compared between probands with BrS/DI-type 1 BrP (n = 257) and control group (n = 370). Lifetime prevalence of migraine was 60.7% in patients with BrS/DI-type 1 BrP and 30.3% in control group (p = 3.6 x 10(-14)). on stepwise regression analysis, familial migraine (odds ratio [OR] of 4.4; 95% confidence interval [CI]: 2.0-9.8; p = 1.3 x 10(-4)), vestibular migraine (OR of 5.4; 95% CI: 1.4-21.0); p = .013), migraine with visual aura (OR of 1.8; 95% CI: 1.0-3.4); p = .04) and younger age-at-onset of migraine (OR of 0.95; 95% CI: 0.93-0.98); p = .004) were predictors of underlying BrS/DI-type 1 BrP among migraineurs. Use of anti-migraine drugs classified as "to be avoided" or "preferably avoided" in patients with BrS and several other anti-migraine drugs with potential cardiac I-Na/I-Ca channel blocking properties was present in 25.6% and 26.9% of migraineurs with BrS/DI-type 1 BrP, respectively. Conclusion Migraine comorbidity is common in patients with BrS/DI-type 1 BrP. We identify several clinical variables that point to an underlying type-1 BrP among migraineurs, necessitating cautious use of certain anti-migraine drugs.Öğe Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity - implications for mechanistic pharmacokinetics modeling(Nature Publishing Group, 2019) Okyar, Alper; Kumar, Swati A.; Filipski, Elisabeth; Piccolo, Enza; Ozturk, Narin; Xandri-Monje, Helena; Pala, Zeliha; Abraham, Kristin; Gomes, Ana Rita Gato de Jesus; Orman, Mehmet N.; Li, Xiao-Mei; Dallmann, Robert; Levi, Francis; Ballesta, AnnabelleP-glycoprotein (P-gp) largely influences the pharmacokinetics (PK) and toxicities of xenobiotics in a patient-specific manner so that personalized drug scheduling may lead to significant patient's benefit. This systems pharmacology study investigated P-gp activity in mice according to organ, sex, feeding status, and circadian time. Sex-specific circadian changes were found in P-gp ileum mRNA and protein levels, circadian amplitudes being larger in females as compared to males. Plasma, ileum and liver concentrations of talinolol, a pure P-gp substrate, significantly differed according to sex, feeding and circadian timing. A physiologically-based PK model was designed to recapitulate these datasets. Estimated mesors (rhythm-adjusted mean) of ileum and hepatic P-gp activity were higher in males as compared to females. Circadian amplitudes were consistently higher in females and circadian maxima varied by up to 10 h with respect to sex. Fasting increased P-gp activity mesor and dampened its rhythm. Ex-vivo bioluminescence recordings of ileum mucosae from transgenic mice revealed endogenous circadian rhythms of P-gp protein expression with a shorter period, larger amplitude, and phase delay in females as compared to males. Importantly, this study provided model structure and parameter estimates to refine PK models of any P-gp substrate to account for sex, feeding and circadian rhythms.Öğe Temel bilgisayar eğitiminde ince istemci sistemlerinin kullanımı(Ege Üniversitesi, 2011) Liv, Kamil Saffet; Orman, Mehmet N.Bilgisayar egitimi günümüz yasantısının ayrılmaz bir parçası haline gelmistir. Bugün içinde bilgisayar sistemlerini barındırmayan hemen hemen hiç bir alan kalmamıs gibidir. Böyle bir ortamda bir üniversite ögrencisinin hiç bir bilgisayar egitimini almadan okulundan mezun olması o ögrenci için büyük bir dezavantaj olacaktır. Bu nedenle tüm üniversitelerde oldugu gibi Ege Üniversitesinde de temel bilgisayar egitimi mecburidir. Bununla beraber temel bilgisayar egitimi uygulamalı bir egitim seklidir ve her ögrenci bu egitimi bir bilgisayar sistemi karsısında almak zorundadır. Temel bilgisayar egitimi teorik ders olarak toplam egitim süresinin küçük bir kesrini isgal edebilir. Günümüzde her ögrenci için bir bilgisayar kesinlikle lüks olmaktan çıkıp gereksinim haline gelmistir. Bu nedenle bu egitimi veren her kurum ögrencinin bu egitimi alması için gerekli olan alt yapıyı saglamak zorundadır. Bu alt yapı temelde donanım ve yazılım olmak üzere iki bilesenden olusmaktadır. Bu iki alanda egitim kurumlarında aranan özellikler kullanılabilirlik, süreklilik kısaca fiyat performans degerleridir. Yazılım alanında bir egitim kurumu olarak üniversiteler mümkün oldugunca açık kaynak kodlu sistemleri tercih etmelidirler. Örnek olarak isletim sistemlerinde "Pardus", "Ubuntu", "Debian", gibi linux tabanlı isletim sistemlerini, ofis çözümlerinde de "open office" gibi yazılımları kullanmalıdırlar. Yazılım seçimi donanım seçimine göre daha sıkıntılı bir süreçtir. Ege Üniversitesi Tıp Fakültesi olarak, her geçen yıl artan ögrenci sayısını da göz önüne alarak temel bilgisayar egitiminde uzun soluklu bir çözümü planlamak kaçınılmaz olmustur. Bu egitimi üstlenen Biyoistatistik ve Tıbbi Bilisim Anabilim Dalı olarak "Temel Bilgisayar Egitiminde nce stemci Sistemlerinin Kullanımı" projesini konun çözümü olarak görmekteyiz.
